ArticleCancer discovery2026
The Molecular and Functional Landscape of Resistance to FOLFIRI Chemotherapy in Metastatic Colorectal Cancer.
Article in Cancer discovery, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
4 citing papers in PubMed.
- Circulating tumor DNA-guided de-escalation or escalation of adjuvant therapy in high-risk stage II and stage III colon cancer: the phase 2 PEGASUS trial.Nature cancer · 2026Article
- Mechanisms and advances of drug resistance in colorectal cancer: A systematic overview of multi-layered regulatory networks.Translational oncology · 2026Review
- A translational colorectal cancer organoid biobank mirrors patients' tumor histology, molecular profiles, and treatment responses.Journal of experimental & clinical cancer research : CR · 2026Article
- The research landscape and future of targeting super-enhancers for cancer therapy: a bibliometric analysis.Discover oncology · 2026Article
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Authors and funding
37 authors.
Funding
Abstract
The combination of 5-fluorouracil and irinotecan (FOLFIRI) remains a standard-of-care treatment for metastatic colorectal cancer (mCRC) yet benefits only about half of patients. Using patient-derived xenografts, we investigated the biological underpinnings of this heterogeneous response. FOLFIRI-resistant models showed transcriptional upregulation of innate immunity and mitochondrial metabolism genes, together with reduced expression of the DNA polymerase POLD1. Sensitive counterparts exhibited a BRCAness-like phenotype with genomic scars of homologous recombination (HR) deficiency, not caused by genetic or epigenetic loss of HR genes but by low abundance of the RAD51 recombinase. In tumoroids, forced RAD51 overexpression attenuated HR deficiency-related scars and chemotherapy-induced damage, whereas HR inhibition through ATM blockade enhanced drug sensitivity. The predictive relevance of key response determinants was validated in clinical samples. This work illuminates functional, nongenetic facets of BRCAness in mCRC and introduces actionable biomarkers and targets, offering prospects to improve clinical decision-making and broaden therapeutic options for chemorefractory patients. SIGNIFICANCE: FOLFIRI response biomarkers in mCRC are lacking. Evidence in patient-derived xenografts, tumoroids, and patients shows that chemosensitivity arises from functional relaxation, rather than (epi)genetic inactivation, of the HR DNA repair pathway. Integrative analyses yield a chemopredictive algorithm centered on the expression of the RAD51 recombinase, with potential to refine patient stratification.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.